Liver damage from flucloxacillin, cloxacillin and dicloxacillin

Olsson, Rolf; Wiholm, Bengt‐Erik; Sand, Crystal; Zettergren, L; Hultcrantz, Rolf; Myrhed, M

doi:10.1016/0168-8278(92)90029-o

Cited by 133 publications

(115 citation statements)

References 15 publications

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“…The mortality rate of 5.4% among patients suffering from flucloxacillin-induced liver injury is in line with previous reports from Sweden and Australia. [29][30][31][32] In a recent study from Japan, age was not found to differ between patients with DILD who developed fulminant hepatic failure versus those who did not. 33 However, in the current study, nonsurvivors with the HC type of DILD were significantly older than those who recovered.…”

Section: Discussionmentioning

confidence: 99%

Outcome and prognostic markers in severe drug‐induced liver disease†

2005

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Section: Discussionmentioning

confidence: 99%

Outcome and prognostic markers in severe drug‐induced liver disease†

2005

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“…A few drugs, such as isoniazid flucloxacillin, halothane, amoxicillin/clavulanate, and nitrofurantoin, were reported to increase the risk of iDILI in older individuals 3, 4, 5, 6, 7. In female patients, there are some trends in the patterns of injury, with hepatocellular as well as autoimmune‐like injury being common 8.…”

Section: Diagnosis Of Idilimentioning

confidence: 99%

Idiosyncratic drug‐induced liver injury: A short review

Yamashita

Imai

Mima

et al. 2017

Hepatology Communications

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Idiosyncratic drug‐induced liver injury (iDILI) is a rare adverse drug reaction that occasionally leads to acute liver failure or even death. An aging population that uses more drugs, a constant influx of newly developed drugs, and a growing risk from herbal and dietary supplements of uncertain quality can lead to an increase in iDILI. Antimicrobials, central nervous system agents, and herbal and dietary supplements are the most common causes of iDILI in developed countries. iDILI is still a diagnosis of exclusion, and thus careful history taking and thorough work‐ups for competing etiologies, such as acute viral hepatitis, autoimmune hepatitis, and others, are essential. The pathogenesis of iDILI is not clear and includes a mix of host reactions, drug metabolites, and environmental factors. Immediate cessation of the suspected offending drug is key to preventing or minimizing progressive damage. No definitive therapies for iDILI are available, and the treatments remain largely supportive. (Hepatology Communications 2017;1:494–500)

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“…Serious skin reactions, including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported through postmarketing surveillance in patients receiving valdecoxib, although it is at present unknown what the root cause to these adverse drug reactions is (Ziemer et al, 2007). Even for the oxacillin derivatives, adverse drug reactions have been reported (Olsson et al, 1992;Andrews and Daly, 2008). Liver injuries have been observed, as well as possible immunoallergic idiosyncratic reactions.…”

Section: Introductionmentioning

confidence: 99%

Novel Bioactivation Mechanism of Reactive Metabolite Formation from Phenyl Methyl-Isoxazoles

et al. 2012

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ABSTRACT:Recently, we described a series of phenyl methyl-isoxazole derivatives as novel, potent, and selective inhibitors of the voltage-gated sodium channel type 1.7 (Bioorg Med Chem Lett 21:3871-3876, 2011). The lead compound, 2-chloro-6-fluorobenzyl [3-(2,6-dichlorophenyl)-5-methylisoxazol-4-yl]carbamate, showed unprecedented GSH and cysteine reactivity associated with NADPH-dependent metabolism in trapping studies using human liver microsomes. Additional trapping experiments with close analogs and mass spectra and NMR analyses suggested that the conjugates were attached directly to the 5-methyl on the isoxazole moiety. We propose a mechanism of bioactivation via an initial oxidation of the 5-methyl generating a stabilized enimine intermediate and a subsequent GSH attack on the 5-methylene. Efforts to ameliorate reactive metabolite generation were undertaken to minimize the potential risk of toxicity. Formation of reactive metabolites could be significantly reduced or prevented by removing the 5-methyl, by N-methylation of the carbamate; by replacing the nitrogen with a carbon or removing the nitrogen to obtain a carboxylate; or by inserting an isomeric 5-methyl isoxazole. The effectiveness of these various chemical modifications in reducing GSH adduct formation is in line with the proposed mechanism. In conclusion, we have identified a novel mechanism of bioactivation of phenyl 5-methylisoxazol-4-yl-amines. The reactivity was attenuated by several modifications aimed to prevent the emergence of an enimine intermediate. Whether 5-methyl isoxazoles should be considered a structural alert for potential formation of reactive metabolites is dependent on their context, i.e., 4-nitrogen.

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Liver damage from flucloxacillin, cloxacillin and dicloxacillin

Cited by 133 publications

References 15 publications

Outcome and prognostic markers in severe drug‐induced liver disease†

Outcome and prognostic markers in severe drug‐induced liver disease†

Idiosyncratic drug‐induced liver injury: A short review

Novel Bioactivation Mechanism of Reactive Metabolite Formation from Phenyl Methyl-Isoxazoles

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